Menopause is associated with an increased risk for a number of medical conditions, including osteoporosis, hot flushes and compromised endothelial function. Currently available treatments for postmenopausal osteoporosis include hormone replacement therapy, calcitonin, bisphosphonates and the selective estrogen receptor modulator, raloxifene.
Unfortunately, these treatments suffer from a number of drawbacks. For example, hormone replacement therapy is associated with an increased risk of breast, endometrial and ovarian cancer, cardiovascular disease, venous thromboembolism and stroke. Bisphosphonates are a front line therapy against osteoporosis, but can cause tremendous esophogeal and gastrointestinal complications, and have been associated with the development of osteonecrosis of the jaw. In addition, the efficacy of bisphosphonates may plateau after chronic use, despite ongoing bone loss, as shown by Ensrud et al. (J Bone Miner Res. 2004; 19(8):1259-69) who reported that alendronate provides no benefit at reducing fractures beyond 5 years of treatment. The reason for this bone loss is the degradation of the body's ability to make new bone, known as bone formation.
Genistein is an aglycone phytoestrogen found in soy and soy products. From epidemiological studies, it has been credited with a number of beneficial health effects in Asian populations including reduced risk of fracture and breast cancer and a lowered risk of cardiovascular dysfunction. Genistein is classified as an isoflavone and it structurally resembles 17-beta estradiol, although its pharmacological profile is somewhat different from that of endogenous estrogens. Highly purified genistein aglycone from soy has undergone testing in preclinical and randomized clinical trials to ascertain its effects on bone health, menopausal symptoms, and cardiovascular function. Morabito et al. (2002) reported the results of a study in which genistein administered for one year to post-menopausal women was shown to improve bone mineral density as well as several biochemical markers of bone health. (Morabito et al., J Bone Miner Res. 2002; 17:1904-12).
Dietary supplements have also been proposed for the maintenance of osteoporotic health, including zinc, vitamin D3, vitamin K, and calcium. Yamaguchi et al. have published several articles and obtained at least one United States patent demonstrating a synergistic relationship between genistein and zinc against various markers of bone metabolism. See U.S. Pat. No. 5,935,996.
Vitamin D3 deficiency is known to cause or contribute to several bone diseases including: Rickets, a childhood disease characterized by impeded growth, and deformity, of the long bones; Osteomalacia, a bone-thinning disorder that occurs exclusively in adults and is characterized by proximal muscle weakness and bone fragility; and Osteoporosis, a condition characterized by reduced bone mineral density and increased bone fragility. (Grant et al., Altern Med Rev 2005; 10 (2): 94-111) As a consequence, much has been written about the importance of vitamin D3 for bone health, but there has been little conclusive evidence concerning its effectiveness in supporting bone health in patients who are not deficient in the vitamin.
Several studies have concluded that vitamin D3 has no effect when combined with other agents such as the bisphosphonates or hormone replacement therapy. Cooper et al., in Am J Clin Nutr 2003; 77(5) 1324-1329, reported that in younger postmenopausal women (age: 56 y), whose average vitamin D3 metabolite concentration was well within the normal range, the addition of 10 000 U vitamin D3/wk to calcium supplementation at 1000 mg/d did not confer benefits on bone mineral density beyond those achieved with calcium supplementation alone. Tuppurainen et al., in Osteoporos Int. 1998; 8(1):32-8, reported that there were no statistically significant improvement in lumbar or femoral bone mineral density changes when vitamin D3 was added to estrogen therapy. Therefore, there appears to be little additional benefit to supplemental vitamin D3 once a threshold serum concentration is achieved.
Nevertheless, the literature is replete with suggestions that vitamin D3 assists in various metabolic functions, including helping to maintain calcium balance (Holick M F, Am J Clin Nutr. 2004; 79(3):362-371), as an aid to cell differentiation (Id.), a booster for the immune system (Griffin M D et al., Annu. Rev. Nutr. 2003; 23:117-145), insulin secretion (Zeitz U et al., FASEB J. 2003; 17(3):509-511), and blood pressure regulation (Sigmund C D, J Clin Invest. 2002; 110(2):155-156). All of these metabolic functions can become compromised as a person ages, and would benefit from vitamin D3 supplementation.